A Study of Ramucirumab in Participants With Metastatic Renal Cell Carcinoma

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00515697
• Collaborator: (none)
• Enrollment: 39
• Locations: 11
• Arm: 1
• Duration (Months): 42
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether ramucirumab is effective treatment in participants with metastatic renal cell carcinoma who have developed progressive disease or become intolerant to tyrosine kinase inhibitor therapy.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Renal Cell Carcinoma	Biological: Ramucirumab	Phase 2

Detailed Description

The Primary objective is to determine the best objective response rate (ORR) of ramucirumab when administered to participants with metastatic renal cell carcinoma (RCC) whose disease has progressed during therapy with a tyrosine kinase inhibitor (TKI, sunitinib and/or sorafenib) or who have developed intolerance to these agents.

Study Design

• Study Type: Interventional
• Actual Enrollment: 39 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Single Arm Study of IMC-1121B in Patients With Metastatic Renal Cell Carcinoma With Disease Progression on or Intolerance to Tyrosine Kinase Inhibitor Therapy
• Study Start Date: Nov 1, 2007
• Actual Primary Completion Date: May 1, 2011
• Actual Study Completion Date: May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ramucirumab Intravenous infusion at 8 milligrams per kilogram (mg/kg) on day 1 of every 14-day cycle.	Biological: Ramucirumab; Ramucirumab is an injectable solution administered as an intravenous infusion over 1 hour at a dose of 8 mg/kg day 1 of every 14-day cycle.; Other Names: IMC-1121B LY3009806

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Objective Response (Objective Response Rate) [First dose to date of objective progressive disease or death due to any cause (up to 34 months)]

   The percentage of participants with a best overall response of confirmed complete response (CR) or partial response (PR) as classified according to Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. CR is the disappearance of all target and non-target lesions and normalization of tumor marker levels. PR is having at least a 30% decrease in the sum of the longest diameter of target lesions without new lesions and progression of non-target lesions. The percentage of participants with objective response=(number of participants whose best overall response during therapy is CR or PR/number of participants treated)*100.

Secondary Outcome Measures

1. Progression-Free Survival [First dose to measured progressive disease or death due to any cause (up to 34 months)]

   Progression-free survival (PFS) is measured from the date of the first dose to the first documented date of disease progression as classified according to Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria or death from any cause. Disease progression is having at least a 20% increase in the sum of the longest diameter of target lesions and/or unequivocal progression of a non-target lesion and/or detection of a new lesion. Data for participants whose disease does not progress or for whom no post-baseline assessment is made are censored at the day of their last tumor assessment. Data for participants whose disease does not progress who are subsequently lost to follow-up are also censored at the day of their last tumor assessment.

2. Percentage of Participants Showing Disease Control at Week 12 [Week 12 [Cycle 6 (1 cycle=14 days)]]

   Participants who were alive and did not experience disease progression were considered to have disease control at 12 weeks. Disease control was based on lack of disease progression using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. According to RECIST criteria, disease progression was having at least a 20% increase in the sum of the longest diameter of target lesions and/or unequivocal progression of non-target lesion and/or detection of new lesion. Participants whose disease progression was symptomatic were not considered to have disease control. The percentage of participants showing disease control=(number of participants who did not have disease or symptomatic progression at Week 12/number of participants treated)*100.

3. Percentage of Participants With Objective Response (Objective Response Rate) at 12 Weeks [Week 12 [Cycle 6 (1 cycle=14 days)]]

   The percentage of participants with a confirmed best overall response of complete response (CR) or partial response (PR) at Week 12, as classified according to Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. CR is the disappearance of all target and non-target lesions and the normalization of tumor marker levels. PR is having at least a 30% decrease in the sum of the longest diameter of target lesions without new lesions and progression of non-target lesions. The percentage of participants with objective response=(number of participants whose best overall response achieved at 12 weeks was CR or PR/number of participants treated)*100.

4. Median Duration of Overall Response [Time of first response (CR or PR) to disease progression, initiation of other (or additional) antitumor therapy, or death due to any cause (up to 34 months)]

   Duration of response is the interval from the date of initial documented response [confirmed complete response (CR) or partial response (PR)] to the first documented date of disease progression as classified according to Response Evaluation Criteria In Solid Tumors (RECIST version 1.0) criteria, or initiation of other (or additional) antitumor therapy is first reported, or death due to any cause. CR is the disappearance of all target and non-target lesions and the normalization of tumor marker levels. PR is having at least a 30% decrease in the sum of the longest diameter of target lesions without new lesions and progression of non-target lesions. Disease progression is having at least a 20% increase in the sum of the longest diameter of target lesions and/or unequivocal progression of a non-target lesion and/or detection of a new lesion. Data from participants who did not relapse were censored on the day of their last tumor assessment.

5. Minimum Concentration (Cmin) of Ramucirumab [Immediately prior to the Week 32 infusion treatment [Cycle 16 (1 cycle=14 days)]]

6. Maximum Concentration (Cmax) of Ramucirumab [1 hour after the end of the Week 32 infusion treatment [Cycle 16 (1 cycle=14 days)]]

7. Summary Listing of Participants Reporting Drug-Related Treatment-Emergent Adverse Events [First dose to study completion (up to 34 months) plus 30-day safety follow-up]

   Data presented are the number of participants who experienced treatment-emergent adverse events (TEAE), serious adverse events (SAE), Grade 3 or 4 TEAE, or adverse events (AE) leading to discontinuation of treatment that were considered to be related to ramucirumab. A summary of SAEs and other nonserious AEs, regardless of causality, is located in the Reported Adverse Events section.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• The participant has histologically or cytologically confirmed clear cell RCC

• The participant is ≥ 18 years of age

• The participant has an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1 or Karnofsky Performance Status (KPS) ≥ 80%

• The participant has had a prior nephrectomy (as therapy for RCC)

• The participant has metastatic RCC

• The participant has a life expectancy of > 3 months

• The participant has measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST)

• The participant has received prior therapy with a TKI (sunitinib and/or sorafenib) with either disease progression on TKI therapy (progression within 60 days of the last dose of TKI) or intolerance to TKI (unable to continue therapy because of side-effects). A participant with progression during a protracted treatment break is not eligible unless the participant has had progression or intolerance as defined above

• The participant has resolution of all clinically significant toxic effects of prior cancer therapy to grade ≤ 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0 (NCI-CTCAE)

• The participant has adequate hematological functions [absolute neutrophil count (ANC) ≥ 1500 cells per milliliter (cells/mL), hemoglobin ≥ 9 grams per deciliter (g/dL) and platelets ≥ 100,000 cells/mL]

• The participant has adequate hepatic function [bilirubin within normal limits (WNL), aspartate transaminase (AST) and/or alanine transaminase (ALT) ≤ 2.5 times the upper limit of normal (ULN), or ≤ 5.0 times the ULN if the transaminase elevation is due to liver metastases]

• The participant has normal renal function or mild renal dysfunction [creatinine ≤ 2.2 milligrams per deciliter (mg/dL)]

• The participant's urinary protein ≤ 1+ on dipstick or routine urinalysis [(UA); if urine dipstick or routine analysis is ≥ 2+, a 24-hour urine for protein must demonstrate < 1000 (milligrams) mg of protein in 24 hours to allow participation in the study]

• The participant must have adequate coagulation function as defined by International Normalized Ratio (INR) ≤ 1.8 and a partial thromboplastin time (PTT) ≤ 1.5 X ULN. Participants on full-dose anticoagulation must be on a stable dose of oral anticoagulant or low molecular weight (LMW) heparin and if on warfarin must have a INR between 2 and 3 and have no active bleeding or pathological condition that carries a high risk of bleeding (for example, tumor involving major vessels or known varices)

• The participant is able to provide informed written consent

• The participant , if sexually active, is postmenopausal (last menstrual period > 2 years prior to study), surgically sterile, or is using effective method of contraception in the opinion of the investigator

• The participant , if female, must have a negative serum pregnancy test upon entry into this study

• The participant has a normal thyroid stimulating hormone (TSH) value. Participants with an abnormal TSH may be eligible provided they meet all other eligibility criteria and have ECOG performance status 0-1. Participants with an abnormal TSH value require a full thyroid evaluation prior to enrollment. Endocrinology consultation may be performed at the discretion of the investigator

• The participant has serum calcium within normal limits

Exclusion Criteria:

• The participant has received prior treatment with bevacizumab

• The participant has known brain or leptomeningeal metastases

• The participant has received >2 prior cytotoxic chemotherapy regimens for RCC

• The participant has received antitumor therapy (biologic agents, major surgery, or investigational agent) within 28 days prior to enrollment on study. The participant has received radiation therapy within 14 days prior to enrollment on study. Participants with metastasis in weight bearing bones at high risk for pathologic fracture may participate provided that appropriate surgical intervention and/or radiation therapy is undertaken and completed at least 28 days prior to enrollment

• The participant has received > 1 prior bio-immunotherapy regimens (defined as either interleukin-2 or interferon alpha given as monotherapy, concurrently, or sequentially as planned)

• The participant has a concurrent active malignancy other than adequately treated non-melanomatous skin cancer or other non-invasive carcinoma or in situ neoplasm. A participant with previous history of malignancy is eligible, provided that he/she has been disease free for > 3 years

• The participant has a nonhealing wound or ulcer

• The participant has a known alcohol or drug dependency

• The participant is pregnant or breastfeeding

• The participant has a coexisting medical or psychiatric problem of sufficient severity to limit compliance with the study and/or increase the risks associated with study participation or study drug administration or interfere with the interpretation of study results

• The participant has an ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, psychiatric illness/social situations, or any other serious uncontrolled medical disorders in the opinion of the investigator

• The participant has known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	ImClone Investigational Site	San Francisco	California	United States	94115
2	ImClone Investigational Site	Chicago	Illinois	United States	60637
3	ImClone Investigational Site	Metairie	Louisiana	United States	70006
4	ImClone Investigational Site	Boston	Massachusetts	United States	02115
5	ImClone Investigational Site	Flemington	New Jersey	United States	08822
6	ImClone Investigational Site	Buffalo	New York	United States	14263
7	ImClone Investigational Site	Cleveland	Ohio	United States	44195
8	ImClone Investigational Site	Drexel Hill	Pennsylvania	United States	19026
9	ImClone Investigational Site	Philadelphia	Pennsylvania	United States	19111
10	ImClone Investigational Site	Arlington	Texas	United States	76012
11	ImClone Investigational Site	Seattle	Washington	United States	98109

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT00515697
• Other Study ID Numbers: 13921; I4T-IE-JVBP; CP12-0605
• First Posted: Aug 14, 2007
• Last Update Posted: Jun 18, 2014
• Last Verified: May 1, 2014

• Additional relevant MeSH terms: Carcinoma; Carcinoma, Renal Cell; Ramucirumab

Study Results

Participant Flow

Pre-assignment Detail	This study comprised 3 study periods: pretreatment, treatment, and (posttreatment) follow-up. 40 participants signed the informed consent.

Arm/Group Title	Ramucirumab
Arm/Group Description	Ramucirumab at 8 milligrams per kilogram (mg/kg) infused intravenously over 1 hour, on Day 1 of every 14-day cycle. Treatment continued until there was evidence of disease progression or intolerable toxicity.
Period Title: Overall Study
STARTED	39
Received at Least 1 Dose of Study Drug	39
COMPLETED	39
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Ramucirumab
Arm/Group Description	Ramucirumab at 8 milligrams per kilogram (mg/kg) infused intravenously over 1 hour, on Day 1 of every 14-day cycle. Treatment continued until there was evidence of disease progression or intolerable toxicity.
Overall Participants	39
Age, Customized (participants) [Number]
Between 18 and 65 years	27 69.2%
>=65 years	12 30.8%
Sex: Female, Male (Count of Participants)
Female	8 20.5%
Male	31 79.5%
Race/Ethnicity, Customized (participants) [Number]
White	35 89.7%
Black or African American	3 7.7%
Asian	1 2.6%
American Indian or Alaska Native	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
More than one race	0 0%
Region of Enrollment (participants) [Number]
United States	39 100%
Ethnicity (participants) [Number]
Hispanic or Latino	1 2.6%
Not Hispanic or Latino	38 97.4%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Objective Response (Objective Response Rate)
Description	The percentage of participants with a best overall response of confirmed complete response (CR) or partial response (PR) as classified according to Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. CR is the disappearance of all target and non-target lesions and normalization of tumor marker levels. PR is having at least a 30% decrease in the sum of the longest diameter of target lesions without new lesions and progression of non-target lesions. The percentage of participants with objective response=(number of participants whose best overall response during therapy is CR or PR/number of participants treated)*100.
Time Frame	First dose to date of objective progressive disease or death due to any cause (up to 34 months)

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: participants who received any quantity of ramucirumab.

Arm/Group Title	Ramucirumab
Arm/Group Description	Ramucirumab at 8 milligrams per kilogram (mg/kg) infused intravenously over 1 hour, on Day 1 of every 14-day cycle. Treatment continued until there was evidence of disease progression or intolerable toxicity.
Measure Participants	39
Number (95% Confidence Interval) [percentage of participants]	5.1 13.1%

2. Secondary Outcome

Title	Progression-Free Survival
Description	Progression-free survival (PFS) is measured from the date of the first dose to the first documented date of disease progression as classified according to Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria or death from any cause. Disease progression is having at least a 20% increase in the sum of the longest diameter of target lesions and/or unequivocal progression of a non-target lesion and/or detection of a new lesion. Data for participants whose disease does not progress or for whom no post-baseline assessment is made are censored at the day of their last tumor assessment. Data for participants whose disease does not progress who are subsequently lost to follow-up are also censored at the day of their last tumor assessment.
Time Frame	First dose to measured progressive disease or death due to any cause (up to 34 months)

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: participants who received any quantity of ramucirumab. The number of participants censored was 4.

Arm/Group Title	Ramucirumab
Arm/Group Description	Ramucirumab at 8 milligrams per kilogram (mg/kg) infused intravenously over 1 hour, on Day 1 of every 14-day cycle. Treatment continued until there was evidence of disease progression or intolerable toxicity.
Measure Participants	39
Median (95% Confidence Interval) [months]	7.1

3. Secondary Outcome

Title	Percentage of Participants Showing Disease Control at Week 12
Description	Participants who were alive and did not experience disease progression were considered to have disease control at 12 weeks. Disease control was based on lack of disease progression using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. According to RECIST criteria, disease progression was having at least a 20% increase in the sum of the longest diameter of target lesions and/or unequivocal progression of non-target lesion and/or detection of new lesion. Participants whose disease progression was symptomatic were not considered to have disease control. The percentage of participants showing disease control=(number of participants who did not have disease or symptomatic progression at Week 12/number of participants treated)*100.
Time Frame	Week 12 [Cycle 6 (1 cycle=14 days)]

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: participants who received any quantity of ramucirumab.

Arm/Group Title	Ramucirumab
Arm/Group Description	Ramucirumab at 8 milligrams per kilogram (mg/kg) infused intravenously over 1 hour, on Day 1 of every 14-day cycle. Treatment continued until there was evidence of disease progression or intolerable toxicity.
Measure Participants	39
Number (95% Confidence Interval) [percentage of participants]	64.1 164.4%

4. Secondary Outcome

Title	Percentage of Participants With Objective Response (Objective Response Rate) at 12 Weeks
Description	The percentage of participants with a confirmed best overall response of complete response (CR) or partial response (PR) at Week 12, as classified according to Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. CR is the disappearance of all target and non-target lesions and the normalization of tumor marker levels. PR is having at least a 30% decrease in the sum of the longest diameter of target lesions without new lesions and progression of non-target lesions. The percentage of participants with objective response=(number of participants whose best overall response achieved at 12 weeks was CR or PR/number of participants treated)*100.
Time Frame	Week 12 [Cycle 6 (1 cycle=14 days)]

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: participants who received any quantity of ramucirumab.

Arm/Group Title	Ramucirumab
Arm/Group Description	Ramucirumab at 8 milligrams per kilogram (mg/kg) infused intravenously over 1 hour, on Day 1 of every 14-day cycle. Treatment continued until there was evidence of disease progression or intolerable toxicity.
Measure Participants	39
Number (95% Confidence Interval) [percentage of participants]	0.0 0%

5. Secondary Outcome

Title	Median Duration of Overall Response
Description	Duration of response is the interval from the date of initial documented response [confirmed complete response (CR) or partial response (PR)] to the first documented date of disease progression as classified according to Response Evaluation Criteria In Solid Tumors (RECIST version 1.0) criteria, or initiation of other (or additional) antitumor therapy is first reported, or death due to any cause. CR is the disappearance of all target and non-target lesions and the normalization of tumor marker levels. PR is having at least a 30% decrease in the sum of the longest diameter of target lesions without new lesions and progression of non-target lesions. Disease progression is having at least a 20% increase in the sum of the longest diameter of target lesions and/or unequivocal progression of a non-target lesion and/or detection of a new lesion. Data from participants who did not relapse were censored on the day of their last tumor assessment.
Time Frame	Time of first response (CR or PR) to disease progression, initiation of other (or additional) antitumor therapy, or death due to any cause (up to 34 months)

Outcome Measure Data

Analysis Population Description

Participants who received any quantity of ramucirumab and had confirmed complete response or partial response. The number of participants censored was 1.

Arm/Group Title	Ramucirumab
Arm/Group Description	Ramucirumab at 8 milligrams per kilogram (mg/kg) infused intravenously over 1 hour, on Day 1 of every 14-day cycle. Treatment continued until there was evidence of disease progression or intolerable toxicity.
Measure Participants	2
Median (95% Confidence Interval) [months]	NA

6. Secondary Outcome

Title	Minimum Concentration (Cmin) of Ramucirumab
Time Frame	Immediately prior to the Week 32 infusion treatment [Cycle 16 (1 cycle=14 days)]

Outcome Measure Data

Analysis Population Description

Participants who received any quantity of ramucirumab and had evaluable pharmacokinetic data at the specified time point.

Arm/Group Title	Ramucirumab
Arm/Group Description	Ramucirumab at 8 milligrams per kilogram (mg/kg) infused intravenously over 1 hour, on Day 1 of every 14-day cycle. Treatment continued until there was evidence of disease progression or intolerable toxicity.
Measure Participants	11
Mean (Standard Deviation) [micrograms per milliliter (mcg/mL)]	147 (76.2)

7. Secondary Outcome

Title	Maximum Concentration (Cmax) of Ramucirumab
Time Frame	1 hour after the end of the Week 32 infusion treatment [Cycle 16 (1 cycle=14 days)]

Outcome Measure Data

Analysis Population Description

Participants who received any quantity of ramucirumab and had evaluable pharmacokinetic data at the specified time point.

Arm/Group Title	Ramucirumab
Arm/Group Description	Ramucirumab at 8 milligrams per kilogram (mg/kg) infused intravenously over 1 hour, on Day 1 of every 14-day cycle. Treatment continued until there was evidence of disease progression or intolerable toxicity.
Measure Participants	9
Mean (Standard Deviation) [micrograms per milliliter (mcg/mL)]	595 (239)

8. Secondary Outcome

Title	Summary Listing of Participants Reporting Drug-Related Treatment-Emergent Adverse Events
Description	Data presented are the number of participants who experienced treatment-emergent adverse events (TEAE), serious adverse events (SAE), Grade 3 or 4 TEAE, or adverse events (AE) leading to discontinuation of treatment that were considered to be related to ramucirumab. A summary of SAEs and other nonserious AEs, regardless of causality, is located in the Reported Adverse Events section.
Time Frame	First dose to study completion (up to 34 months) plus 30-day safety follow-up

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: participants who received any quantity of ramucirumab.

Arm/Group Title	Ramucirumab
Arm/Group Description	Ramucirumab at 8 milligrams per kilogram (mg/kg) infused intravenously over 1 hour, on Day 1 of every 14-day cycle. Treatment continued until there was evidence of disease progression or intolerable toxicity.
Measure Participants	39
Related TEAE	37 94.9%
Related SAE	6 15.4%
Related Grade 3 or 4 TEAE	10 25.6%
Related AE leading to discontinuation	7 17.9%

Adverse Events

Arm/Group Title	Ramucirumab
Arm/Group Description	Ramucirumab at 8 milligrams per kilogram (mg/kg) infused intravenously over 1 hour, on Day 1 of every 14-day cycle. Treatment continued until there was evidence of disease progression or intolerable toxicity.
All Cause Mortality
	Ramucirumab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Ramucirumab
	Affected / at Risk (%)	# Events
Total	12/39 (30.8%)
Cardiac disorders
CARDIO-RESPIRATORY ARREST	1/39 (2.6%)	1
MYOCARDIAL INFARCTION	1/39 (2.6%)	1
General disorders
FATIGUE	1/39 (2.6%)	1
MULTI-ORGAN FAILURE	1/39 (2.6%)	1
Infections and infestations
URINARY TRACT INFECTION	1/39 (2.6%)	1
Metabolism and nutrition disorders
ANOREXIA	1/39 (2.6%)	1
Musculoskeletal and connective tissue disorders
BACK PAIN	1/39 (2.6%)	1
Nervous system disorders
ALTERED STATE OF CONSCIOUSNESS	1/39 (2.6%)	1
CEREBRAL ISCHAEMIA	1/39 (2.6%)	1
NEUROPATHY PERIPHERAL	1/39 (2.6%)	1
SPINAL CORD COMPRESSION	1/39 (2.6%)	1
Renal and urinary disorders
HAEMATURIA	1/39 (2.6%)	1
PROTEINURIA	1/39 (2.6%)	1
RENAL FAILURE ACUTE	1/39 (2.6%)	1
Respiratory, thoracic and mediastinal disorders
HAEMOPTYSIS	1/39 (2.6%)	1
Surgical and medical procedures
SPINAL LAMINECTOMY	1/39 (2.6%)	1
Vascular disorders
HYPERTENSIVE CRISIS	1/39 (2.6%)	1
Other (Not Including Serious) Adverse Events
	Ramucirumab
	Affected / at Risk (%)	# Events
Total	39/39 (100%)
Blood and lymphatic system disorders
ANAEMIA	3/39 (7.7%)	3
THROMBOCYTOPENIA	5/39 (12.8%)	8
Eye disorders
VISION BLURRED	2/39 (5.1%)	2
Gastrointestinal disorders
ABDOMINAL DISCOMFORT	2/39 (5.1%)	3
ABDOMINAL PAIN	6/39 (15.4%)	9
CONSTIPATION	8/39 (20.5%)	9
DIARRHOEA	7/39 (17.9%)	16
DYSPEPSIA	2/39 (5.1%)	3
ERUCTATION	2/39 (5.1%)	2
FLATULENCE	2/39 (5.1%)	2
NAUSEA	10/39 (25.6%)	13
TOOTHACHE	2/39 (5.1%)	2
VOMITING	9/39 (23.1%)	10
General disorders
CHILLS	6/39 (15.4%)	7
FACE OEDEMA	2/39 (5.1%)	2
FATIGUE	19/39 (48.7%)	37
INFUSION RELATED REACTION	3/39 (7.7%)	6
OEDEMA PERIPHERAL	14/39 (35.9%)	19
PYREXIA	2/39 (5.1%)	2
Infections and infestations
PHARYNGITIS	3/39 (7.7%)	7
RHINITIS	7/39 (17.9%)	14
SINUSITIS	2/39 (5.1%)	3
UPPER RESPIRATORY TRACT INFECTION	4/39 (10.3%)	5
Injury, poisoning and procedural complications
CONTUSION	3/39 (7.7%)	3
Investigations
BLOOD CREATININE INCREASED	4/39 (10.3%)	5
WEIGHT DECREASED	6/39 (15.4%)	8
WEIGHT INCREASED	3/39 (7.7%)	3
Metabolism and nutrition disorders
ANOREXIA	10/39 (25.6%)	13
DEHYDRATION	2/39 (5.1%)	2
HYPERCALCAEMIA	2/39 (5.1%)	2
HYPERGLYCAEMIA	3/39 (7.7%)	4
HYPERURICAEMIA	2/39 (5.1%)	5
HYPOPHOSPHATAEMIA	3/39 (7.7%)	3
Musculoskeletal and connective tissue disorders
ARTHRALGIA	12/39 (30.8%)	16
BACK PAIN	8/39 (20.5%)	11
BONE PAIN	2/39 (5.1%)	2
FLANK PAIN	2/39 (5.1%)	2
MUSCULOSKELETAL CHEST PAIN	3/39 (7.7%)	4
MYALGIA	4/39 (10.3%)	4
NECK PAIN	2/39 (5.1%)	3
PAIN IN EXTREMITY	4/39 (10.3%)	5
Nervous system disorders
DIZZINESS	4/39 (10.3%)	6
HEADACHE	14/39 (35.9%)	38
NEUROPATHY	2/39 (5.1%)	2
PERIPHERAL SENSORY NEUROPATHY	2/39 (5.1%)	3
SOMNOLENCE	2/39 (5.1%)	2
Psychiatric disorders
ANXIETY	4/39 (10.3%)	4
DEPRESSION	2/39 (5.1%)	3
INSOMNIA	4/39 (10.3%)	4
Renal and urinary disorders
HAEMATURIA	2/39 (5.1%)	2
PROTEINURIA	7/39 (17.9%)	10
RENAL FAILURE ACUTE	2/39 (5.1%)	3
Respiratory, thoracic and mediastinal disorders
COUGH	7/39 (17.9%)	13
DYSPNOEA	7/39 (17.9%)	11
DYSPNOEA EXERTIONAL	2/39 (5.1%)	2
EPISTAXIS	13/39 (33.3%)	19
HAEMOPTYSIS	2/39 (5.1%)	3
NASAL CONGESTION	4/39 (10.3%)	5
PHARYNGOLARYNGEAL PAIN	2/39 (5.1%)	2
Skin and subcutaneous tissue disorders
DERMATITIS ACNEIFORM	2/39 (5.1%)	2
DRY SKIN	5/39 (12.8%)	5
NIGHT SWEATS	2/39 (5.1%)	2
PAIN OF SKIN	2/39 (5.1%)	2
PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME	3/39 (7.7%)	4
PRURITUS	5/39 (12.8%)	11
RASH	4/39 (10.3%)	5
Vascular disorders
HYPERTENSION	7/39 (17.9%)	8

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Investigators agreed to delay independently publishing or disclosing data, findings or conclusions from the study except as part of a multi-center publication. Upon study publication or if the draft publication is not produced within approximately 6 months of the final report of the study results, investigators may independently publish, subject to confidential information review/redaction by sponsor. The sponsor may request publication delay up to 90 days to seek patent protection.